ABSTRACT
Objective To identify susceptible miRNAs for the pathogenesis of diabetic nephropathy (DN) and the molecular targets of losartan treatment. Methods The 8-week age KKAy mice were divided into losartan treatment group (10 mg· kg-1· d-1) and non-treatment group,C57BL/6 mice were used as the control group.At age of 20 weeks,body weight,random blood glucose,urinary albumin and urinary creatinine were tested,and kidney morphology was observed.Glomeroli were separated by magnetic beads perfusion,and total RNA were extracted.MiRNAs expression profiles were analyzed by the Affymetrix GeneChip miRNAs arrays. Results At age of 20 weeks,KKAy mice developed higher body weight,higher blood glucose and higher urinary microalbumin creatinine ratio than C57BL/6 mice,and the glomerular basement membrane thickened,mesangial matrix widened.Losartan treatment markedly improved the level of urinary albumin creatinine ratio [(539.71±100.23) mg/g vs (728±177.19) mg/g,P＜0.05)] and pathological lesion of KKAy mice.The miRNA array analysis showed that there were 22 miRNAs differentially expressed between KKAy non-treatment mice and C57BL/6 mice glomeruli at age of 20 weeks.Among them,10 miRNAs were up-regulated,and 12 miRNAs were down-regulated.The expression of 4 miRNAs was down-regulated in glumeruli of KKAy mice treated by losartan compared with that of non-treatment mice.The expressions of miRNA-503 and miRNA-181d were significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment, Conclusion The expressions of miRNA-503 and miRNA-181d are significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment,which may be new therapeutic targets of DN.